Corneal Disease (Khurana)

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Corneal Anatomy & Physiology Layers (6): Epithelium: Non-keratinized stratified squamous epithelium (5-7 layers). Rapid regeneration (7-10 days). Contains microvilli that interdigitate with tear film mucin layer. Possesses tight junctions for barrier function. Bowman's Layer: Acellular, modified superficial stroma (8-14 $\mu m$ thick). Composed of fine collagen fibrils. Does not regenerate; damage results in scarring. Stroma: Accounts for 90% of corneal thickness (500 $\mu m$). Consists of highly organized collagen lamellae (Type I, III, V, VI), keratocytes (modified fibroblasts), and ground substance (proteoglycans like chondroitin sulfate, keratan sulfate). Regular spacing of collagen fibrils is crucial for transparency. Dua's Layer: Recently identified layer between stromal posterior one-third and Descemet's membrane. Strong, acellular, collagenous layer. Descemet's Membrane: Basement membrane of the endothelium (10-15 $\mu m$ thick). Produced by endothelial cells; thickens with age. Composed mainly of Type IV collagen. Elastic properties, resistant to enzymes. Endothelium: Single layer of hexagonal cells (5 $\mu m$ thick). Does not regenerate; cell density decreases with age. Functions as a metabolic pump (Na+/K+ ATPase) to maintain corneal deturgescence (relative dehydration), essential for transparency. Functions: Transparency: Achieved by avascularity, deturgescence, uniform collagen fibril arrangement, smooth epithelial surface (maintained by tear film). Refraction: Primary refracting surface of the eye (~43-45 Diopters). Protection: Physical barrier against trauma and infection. Nerve Supply: Primarily from the ophthalmic division of the trigeminal nerve (V1) via long ciliary nerves. Highest density of sensory nerves in the body, especially in the central cornea. Responsible for reflex tearing and blink. Metabolism: Primarily anaerobic glycolysis (90%) for energy. Glucose from aqueous humor. Oxygen from atmosphere (anterior), aqueous humor (posterior), and limbal vessels. Corneal Ulcers (Infectious Keratitis) 1. Bacterial Corneal Ulcer Etiology/Organisms: Gram-positive: Staphylococcus aureus (most common, especially in contact lens wearers, post-trauma), Streptococcus pneumoniae (often rapid, aggressive, associated with dacryocystitis), Coagulase-negative Staphylococci, Enterococcus . Gram-negative: Pseudomonas aeruginosa (rapidly progressive, severe, often associated with contact lens abuse, produces proteolytic enzymes, greenish discharge), Klebsiella, Enterobacter, Serratia marcescens . Predisposing Factors: Trauma (vegetable matter, foreign body), contact lens wear (poor hygiene, extended wear), ocular surface disease (dry eye, blepharitis, trichiasis, exposure keratopathy), chronic use of topical corticosteroids or NSAIDs, diabetes, systemic immunosuppression. Clinical Features: Symptoms: Severe pain, redness (ciliary injection), photophobia, decreased vision, mucopurulent discharge. Signs: Epithelial Defect: Always present, stains with fluorescein. Stromal Infiltrate: Greyish-white, dense, well-demarcated, often with overlying epithelial defect. Can progress to necrosis. Corneal Edema: Surrounding infiltration. Anterior Chamber Reaction: Flare and cells, often hypopyon (sterile or infective). Associated: Limbal injection, conjunctival chemosis. Severe cases: Descemetocele formation, corneal perforation. Diagnosis: Corneal scraping from the base and margins of the ulcer for Gram stain, KOH mount, and culture (Blood agar, Chocolate agar, Sabouraud's Dextrose Agar). Conjunctival swabs, contact lens case culture. Management: Topical Antibiotics (intensive): Initial: Fortified antibiotics (e.g., Cefazolin 5% or Vancomycin 5% for Gram-positive + Tobramycin 1.3% or Gentamicin 1.3% for Gram-negative). Or monotherapy with a broad-spectrum fluoroquinolone (Moxifloxacin 0.5% or Gatifloxacin 0.5%) every hour. Adjust based on culture/sensitivity: De-escalate as appropriate. Cycloplegics: Atropine 1% or Cyclopentolate 1% (to relieve ciliary spasm, prevent posterior synechiae). Steroids: Generally contraindicated in active bacterial ulcer, may be considered after significant resolution of infection (under strict antibiotic cover) to reduce scarring. Systemic Antibiotics: Rarely required, only for severe cases with scleral extension, endophthalmitis, or impending perforation. Pain Management: Oral analgesics. Surgical: Therapeutic penetrating keratoplasty for impending or actual perforation, intractable infection. 2. Fungal Corneal Ulcer (Keratomycosis) Etiology/Organisms: Filamentous Fungi (Hyalohyphomycetes): Fusarium (tropical, often associated with vegetable matter trauma, contact lens solutions), Aspergillus (common in temperate climates, post-trauma), Curvularia, Penicillium . Yeasts: Candida albicans (more common in compromised corneas, chronic ocular surface disease, steroid use, systemic immunosuppression). Predisposing Factors: Trauma with vegetable matter, agricultural work, contact lens wear, chronic ocular surface disease, topical steroid use, diabetes mellitus. Clinical Features: Symptoms: Pain (less severe than bacterial, often disproportionate to signs), redness, photophobia, decreased vision, often watery or mucoid discharge. Indolent course. Signs: Infiltrate: Greyish-white, often dry, raised, with characteristic "feathery margins" or "satellite lesions" (small infiltrates separated from main lesion). Endothelial Plaque: White plaque on posterior corneal surface. Immune Ring: A ring of immune cells around the infiltrate. Hypopyon: Often dense, sometimes brown/white, non-shifting. Associated: Corneal edema, epithelial defect. Diagnosis: Corneal scraping for KOH mount (branching hyphae), Gram stain, Giemsa stain. Culture on Sabouraud's Dextrose Agar (without cycloheximide), Blood agar. Confocal microscopy can be helpful. Management: Topical Antifungals: Filamentous: Natamycin 5% suspension (drug of choice for superficial filamentous fungi), Voriconazole 1% (compounded). Yeast (Candida): Amphotericin B 0.15% (compounded), Fluconazole 0.2%. Initial frequency: Hourly for 24-48 hours, then tapered. Systemic Antifungals: Voriconazole (oral/IV) or Fluconazole (oral) for deep-seated ulcers, large lesions, or those unresponsive to topical agents. Cycloplegics: Atropine 1% or Cyclopentolate 1%. Debridement: May help remove fungal load and improve drug penetration. Surgery: Therapeutic penetrating keratoplasty for non-healing ulcers, impending perforation, or perforation. 3. Viral Keratitis (Herpes Simplex Keratitis - HSK) Etiology: Herpes Simplex Virus Type 1 (HSV-1) is the most common cause. Primary infection (blepharoconjunctivitis) followed by latent infection in trigeminal ganglion, reactivates due to stress, UV light, fever, trauma, immunosuppression. Clinical Forms: Primary Ocular HSV: Blepharoconjunctivitis (vesicles on lids, follicular conjunctivitis). Recurrent HSK: Epithelial Keratitis: Punctate Epithelial Keratitis: Fine, scattered epithelial lesions. Dendritic Ulcer: Classic branching, linear epithelial defect with characteristic terminal bulbs, stains with fluorescein (epithelial defect) and rose bengal (virus-infected cells at margins). Geographic Ulcer: Enlarged, amoeboid-shaped dendritic ulcer, often seen with topical steroid use. Stromal Keratitis: Immune Stromal Keratitis (Disciform Keratitis): Most common, immune-mediated reaction to viral antigens. Disc-shaped central stromal edema, folds in Descemet's, KPs, mild AC reaction. Intact epithelium. Necrotizing Stromal Keratitis: Direct viral invasion of stroma, severe inflammation, stromal opacification, thinning, necrosis. High risk of perforation. Interstitial Keratitis: Diffuse stromal inflammation, usually non-necrotizing. Endotheliitis: Inflammation of the corneal endothelium, often presenting as KPs and corneal edema. Can be diffuse, linear, or disciform. Neurotrophic Keratopathy: Due to damage to corneal nerves from recurrent infections, leading to reduced corneal sensation, persistent epithelial defects, and ulceration. Diagnosis: Clinical appearance. Corneal scraping for PCR (viral DNA), viral culture, immunofluorescence. Management: Epithelial Keratitis: Topical Antivirals: Acyclovir 3% ophthalmic ointment (5x/day), Ganciclovir 0.15% ophthalmic gel (5x/day). Trifluridine 1% solution (9x/day). Oral Antivirals: Acyclovir (400mg 5x/day), Valacyclovir, Famciclovir for severe or non-responsive cases. Debridement: Mechanical removal of infected epithelium can shorten course. NO STEROIDS in active epithelial disease, as they can worsen the infection (geographic ulcer). Stromal Keratitis/Endotheliitis: Topical Corticosteroids: Prednisolone acetate 1% (tapered slowly over weeks-months). MUST be used under cover of topical or oral antivirals to prevent reactivation of epithelial disease. Antivirals: Oral Acyclovir (400mg BID-TID for prophylaxis) or Valacyclovir/Famciclovir. Topical antivirals are less effective for stromal disease. Cycloplegics: Atropine 1% or Cyclopentolate 1%. Neurotrophic Keratopathy: Lubricants, bandage contact lens, tarsorrhaphy. Prophylaxis: Oral Acyclovir (400mg BID) for patients with recurrent HSK, especially stromal disease. 4. Acanthamoeba Keratitis (AK) Etiology: Free-living protozoan (amoeba) found in soil, water, air. Associated with contact lens wear (poor hygiene, tap water rinse, homemade saline), trauma, contaminated water. Clinical Features: Symptoms: Severe pain disproportionate to clinical signs, redness, photophobia, tearing, decreased vision. Often prolonged diagnosis. Signs: Early: Punctate epithelial erosions, pseudodendrites (look like HSV dendrites but lack terminal bulbs and stain poorly with rose bengal). Classic: Radial perineuritis (inflammation along corneal nerves, appears as fine white lines), leading to ring infiltrate (late stage, immune reaction to amoeba). Stromal infiltrates, anterior uveitis, satellite lesions. Recurrent epithelial breakdown, corneal thinning, scleritis (rare). Diagnosis: Corneal scraping for Giemsa stain (trophozoites, cysts), calcofluor white stain. Culture on non-nutrient agar with an overlay of E. coli or Klebsiella . Confocal microscopy is highly useful for visualizing cysts/trophozoites in vivo. PCR. Management: Intensive Topical Antiprotozoals: Biguanides: Polyhexamethylene Biguanide (PHMB 0.02%) or Chlorhexidine 0.02% (hourly for days/weeks, then tapered slowly over months). Diamidines: Propamidine isethionate 0.1% (Brolene) or Hexamidine 0.1%. Combination therapy (biguanide + diamidine) is often used. Cycloplegics: Atropine 1%. Oral Antifungals: Ketoconazole or Itraconazole may be used as adjunctive therapy in severe cases. Corticosteroids: Generally avoided in active disease, may be considered very late in treatment after significant reduction of organism load to control inflammation. Surgical: Therapeutic penetrating keratoplasty for perforation or medically refractory cases, but recurrence in the graft is common. Duration: Treatment is prolonged, often for several months to a year, due to the resistant cyst form. Corneal Dystrophies Genetically determined, bilateral, usually symmetrical, progressive, non-inflammatory corneal opacities. Classified by anatomical location. Epithelial/Subepithelial Dystrophies: Epithelial Basement Membrane Dystrophy (EBMD) / Map-Dot-Fingerprint Dystrophy / Cogan's Microcystic Dystrophy: Most common. Abnormal basement membrane production leading to intraepithelial cysts, grey maps, and fingerprint lines. Symptoms: Often asymptomatic. Can cause recurrent corneal erosions (pain, photophobia upon waking), fluctuating vision. Management: Lubricants, hypertonic saline, bandage contact lens, anterior stromal puncture, superficial keratectomy, phototherapeutic keratectomy (PTK). Meesmann's Corneal Dystrophy: Numerous tiny, clear intraepithelial cysts, usually asymptomatic or mild irritation. Bowman's Layer Dystrophies: Reis-Bücklers Corneal Dystrophy (RBCD): Subepithelial reticular opacities, severe recurrent erosions in childhood. Significant vision loss. Thiel-Behnke Corneal Dystrophy (TBCD) / Honeycomb Dystrophy: Similar to RBCD but less severe, honeycomb-shaped opacities. Management: PTK, superficial keratectomy, lamellar keratoplasty. Stromal Dystrophies: Lattice Corneal Dystrophy (Type I): Autosomal dominant. Refractile branching lines (amyloid deposits) in superficial to mid-stroma. Recurrent erosions, progressive vision loss. Management: PTK, PK. Granular Corneal Dystrophy (Type I): Autosomal dominant. Well-demarcated, crumb-like, white opacities (hyaline deposits) in central superficial stroma. Clear cornea between opacities. Less severe erosions. Macular Corneal Dystrophy (MCD): Autosomal recessive. Most severe stromal dystrophy. Diffuse, poorly defined grey-white opacities (mucopolysaccharide deposits) throughout the entire stroma, extending to limbus. Corneal edema. Significant vision loss early in life. Management: PK (only effective treatment). Schnyder Crystalline Dystrophy: Cholesterol and lipid crystal deposits in central stroma, often arcus lipoides. Associated with hyperlipidemia. Descemet's Membrane & Endothelial Dystrophies: Fuchs Endothelial Dystrophy: Autosomal dominant, more common in females. Progressive endothelial cell loss and dysfunction, resulting in guttae (exaggerated Descemet's warts) visible on posterior cornea. Leads to stromal edema, epithelial edema, bullous keratopathy. Symptoms: Glare, blurred vision (worse in morning), foreign body sensation. Signs: Corneal guttae, stromal edema, microcystic epithelial edema, bullae. Management: Hypertonic saline drops/ointment (5%), hair dryer (to dehydrate epithelium), bandage contact lens. Surgical: Descemet's Stripping Endothelial Keratoplasty (DSEK) or Descemet's Membrane Endothelial Keratoplasty (DMEK) are preferred over PK. Posterior Polymorphous Corneal Dystrophy (PPCD): Irregular endothelial cells with epithelial-like features. Vesicles, bands, geographic lesions on posterior cornea. Can cause glaucoma. Congenital Hereditary Endothelial Dystrophy (CHED): Bilateral corneal edema present at birth or in early childhood. Autosomal recessive (CHED1, severe) or dominant (CHED2, milder). Management: PK or DMEK/DSEK in infancy/childhood. Corneal Ectasias 1. Keratoconus Progressive, non-inflammatory thinning and steepening of the central or paracentral cornea, leading to a conical protrusion. Associated with eye rubbing, atopy, Down syndrome, Marfan syndrome. Clinical Features: Symptoms: Progressive decrease in vision, frequent changes in spectacle prescription, glare, monocular polyopia. Early Signs: Irregular astigmatism, scissoring reflex on retinoscopy, distorted keratometry mires. Classical Signs: Munson's Sign: V-shaped indentation of the lower eyelid when the patient looks down. Rizzuti's Sign: Conical reflection on the nasal cornea when a penlight is shone from the temporal side. Fleischer's Ring: A brown-yellow-green ring of iron deposition (hemosiderin) in the basal epithelial cells at the base of the cone, best seen with cobalt blue filter. Vogt's Striae: Fine, vertical stress lines in the deep stroma/Descemet's membrane, disappear with external pressure. Apical Scarring: Due to repeated breaks in Bowman's layer. Acute Hydrops: Sudden rupture of Descemet's membrane, allowing aqueous humor to enter the stroma, causing acute corneal edema, pain, and marked vision loss. Resolves spontaneously over weeks-months, leaving a scar. Diagnosis: Corneal Topography/Tomography: Most sensitive for early diagnosis and monitoring progression. Shows localized steepening and thinning. Pachymetry: Measures corneal thickness, typically thinnest at the apex of the cone. Slit Lamp Examination. Management: Corrective (Early): Spectacles, then rigid gas permeable (RGP) contact lenses (to create a new refracting surface). Scleral lenses for advanced cases. Stabilizing (Progression): Corneal Collagen Cross-linking (CXL) with Riboflavin and UV-A light. Strengthens corneal collagen, halts progression. Surgical (Advanced): Intracorneal Ring Segments (ICRS/Intacs): Flatten the cone and reduce astigmatism. Deep Anterior Lamellar Keratoplasty (DALK): Replaces diseased stroma while preserving the patient's healthy Descemet's membrane and endothelium. Preferred over PK if endothelium is healthy, lower rejection risk. Penetrating Keratoplasty (PK): Full-thickness corneal transplant for severe scarring, hydrops, or failed DALK/ICRS. 2. Keratoglobus Rare, non-inflammatory, bilateral condition characterized by generalized diffuse thinning and globular protrusion of the entire cornea. Often congenital. Associations: Ehlers-Danlos syndrome, blue sclera, Leber's congenital amaurosis. Clinical Features: Markedly thinned cornea, often from limbus to limbus. High myopia and astigmatism. High risk of corneal rupture with minor trauma. Management: Protective eyewear, large diameter RGP contact lenses, penetrating keratoplasty (challenging due to large diameter and thin host tissue). 3. Pellucid Marginal Degeneration (PMD) Rare, non-inflammatory, bilateral peripheral corneal thinning, typically inferiorly (1-2 mm from limbus), with an intact epithelium. The cornea above the thinned area protrudes, creating a "beer belly" or "crab claw" appearance on topography. Clinical Features: Progressive irregular astigmatism, against-the-rule astigmatism. Vision loss. Diagnosis: Corneal topography (classic "kissing doves" or "crab claw" pattern). Slit lamp shows clear cornea with peripheral thinning. Management: Spectacles (early), RGP contact lenses (toric, large diameter), scleral lenses. Surgical options: Corneal cross-linking (off-label, often with customized patterns), lamellar keratoplasty, wedge resection. Corneal Degenerations Acquired, often unilateral or asymmetrical, can be inflammatory or non-inflammatory. Not inherited. Arcus Senilis (Corneal Arcus): Very common, bilateral, circumferential lipid deposition (cholesterol, phospholipids, triglycerides) in the peripheral corneal stroma. Clear zone (lucid interval of Vogt) separates it from the limbus. Age-related. If unilateral or in young individuals, investigate for carotid artery disease or hyperlipidemia. Harmless. Band Keratopathy: Deposition of calcium salts (calcium phosphate) in the superficial cornea (Bowman's layer and anterior stroma). Appears as a horizontal greyish-white band, usually with clear areas at 3 and 9 o'clock. Causes: Chronic ocular inflammation (uveitis, glaucoma), hypercalcemia (hyperparathyroidism, sarcoidosis, renal failure), chronic silicone oil in the eye. Management: Chelation with EDTA (ethylenediaminetetraacetic acid) after epithelial debridement. PTK. Pterygium: Wing-shaped fibrovascular growth of conjunctival tissue onto the cornea, typically from the nasal side. Associated with chronic UV exposure, wind, dust. Symptoms: Irritation, redness, foreign body sensation, induced astigmatism, vision obstruction if encroaches on visual axis. Management: Lubricants, mild steroids (for inflammation). Surgical excision with conjunctival autograft or amniotic membrane transplant to prevent recurrence. Salzmann's Nodular Degeneration: Bluish-white or greyish-white, elevated, avascular nodules on the anterior corneal stroma (often over Bowman's layer). Associated with chronic corneal irritation or inflammation. Management: Lubricants, bandage contact lens. Surgical removal (superficial keratectomy) for symptomatic cases or visual impairment. Terrien's Marginal Degeneration: Rare, bilateral, slowly progressive peripheral corneal thinning, usually superiorly, with an intact epithelium. Can lead to lipid deposition and ectasia, often without inflammation. High risk of perforation with minor trauma. Management: Protective eyewear, spectacles, contact lenses. Surgical: Lamellar keratoplasty for thinning/perforation. Corneal Edema Accumulation of fluid in the corneal layers due to disruption of the normal deturgescence mechanism. Causes: Endothelial Dysfunction: Most common. Fuchs' dystrophy, pseudophakic/aphakic bullous keratopathy (after cataract surgery), trauma, acute angle closure glaucoma (due to high IOP). Epithelial Defects: Allowing fluid entry (e.g., abrasions, ulcers). Inflammation: Keratitis, uveitis. Contact Lens Overwear. Clinical Features: Corneal haze (stromal edema), microcystic epithelial edema, bullae formation (epithelial bullous keratopathy), reduced vision, glare, photophobia, pain. Management: Address underlying cause. Hypertonic Saline: 5% drops/ointment (to draw fluid out). Bandage Contact Lens: For bullous keratopathy to relieve pain. Topical Corticosteroids: If inflammatory component. Surgical: DSEK/DMEK or PK for chronic, visually significant endothelial failure. Corneal Trauma Corneal Abrasions: Loss of epithelial cells, usually due to mechanical trauma. Symptoms: Severe pain, foreign body sensation, photophobia, tearing, redness. Signs: Epithelial defect staining with fluorescein. Management: Topical antibiotics (e.g., Moxifloxacin) to prevent infection, cycloplegic (for pain), oral analgesics. Bandage contact lens can provide comfort. Heals rapidly (24-72 hours). Corneal Foreign Body: Embedded particle on or in the cornea. Symptoms: Foreign body sensation, pain, tearing. Signs: Visible foreign body, rust ring (if metallic). Management: Remove with irrigation, cotton-tipped applicator, or sterile needle under slit lamp. Treat as abrasion afterwards. Rust ring may require further removal. Corneal Lacerations/Perforations: Full-thickness injury to the cornea. Ocular emergency. Symptoms: Severe pain, vision loss, gush of fluid (aqueous). Signs: Full-thickness wound, iris prolapse, shallow anterior chamber, positive Seidel test (aqueous leakage). Management: Surgical repair (suturing), topical/systemic antibiotics, cycloplegics. May require PK for large or irregular wounds. Chemical Injuries: Ocular emergency. Severity depends on pH, volume, duration of contact. Alkali burns (e.g., lye, ammonia) are worse than acid burns (e.g., battery acid) as they penetrate deeper. Symptoms: Excruciating pain, redness, vision loss. Signs: Conjunctival chemosis, limbal ischemia (blanching of vessels), corneal edema, opacification, epithelial defect. Management: Immediate and copious irrigation: With saline or water for at least 30 minutes, until pH normalizes. After irrigation: Topical antibiotics, cycloplegics, topical corticosteroids (short-term for inflammation, then carefully to avoid melting), oral Vitamin C (promotes collagen synthesis), topical citrate/acetylcysteine (collagenase inhibitors). Surgical: Amniotic membrane transplantation, limbal stem cell transplantation, keratoplasty for severe cases. Corneal Transplant (Keratoplasty) Surgical replacement of diseased corneal tissue with healthy donor tissue. Penetrating Keratoplasty (PK) / Full-Thickness Keratoplasty: Replacement of the entire thickness of the central cornea. Indications: Keratoconus (advanced), corneal dystrophies (e.g., Macular, advanced Fuchs'), severe corneal scarring, bullous keratopathy (when no suitable endothelial technique is possible), failed previous grafts, therapeutic for intractable infections. Advantages: Long-standing procedure, treats various pathologies. Disadvantages: High astigmatism, prolonged visual recovery, higher risk of graft rejection, wound dehiscence, glaucoma. Lamellar Keratoplasty: Partial-thickness corneal replacement. Deep Anterior Lamellar Keratoplasty (DALK): Replaces diseased anterior corneal stroma and Bowman's layer, preserving the patient's own healthy Descemet's membrane and endothelium. Indications: Keratoconus, stromal dystrophies (Lattice, Granular), stromal scars (if endothelium is healthy). Advantages: Significantly lower risk of endothelial graft rejection, faster visual recovery, better tectonic integrity (stronger globe), no need for donor endothelium. Techniques: Big-bubble technique (injecting air into deep stroma to separate Descemet's), manual dissection. Endothelial Keratoplasty: Replaces only the diseased endothelium and Descemet's membrane. Descemet's Stripping Endothelial Keratoplasty (DSEK) / Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK): Donor tissue includes Descemet's and a thin layer of posterior stroma. Descemet's Membrane Endothelial Keratoplasty (DMEK): Only Descemet's membrane and endothelium are transplanted. Indications: Fuchs' endothelial dystrophy, pseudophakic bullous keratopathy, posterior polymorphous corneal dystrophy. Advantages (DMEK > DSEK > PK): Faster and superior visual recovery, lower rejection rates, minimal induced astigmatism, stronger globe. Disadvantages: Technically more challenging, higher risk of graft detachment (requires re-bubbling). Graft Rejection: Immune-mediated attack on donor tissue, most common cause of graft failure. Risk Factors: Vascularized host cornea, large graft, previous graft failure, young recipient. Types: Epithelial, subepithelial, stromal, endothelial (most common and sight-threatening). Clinical Signs (Endothelial Rejection): Khodadoust Line: A line of KPs migrating across the endothelium. Stromal edema, KPs on the donor endothelium, anterior chamber reaction (flare and cells), graft vascularization. Management: Intensive topical corticosteroids (e.g., Prednisolone acetate 1% hourly), systemic corticosteroids (oral Prednisone), cycloplegics. Early detection and treatment are crucial.